Disseminated trichosporonosis with atypical histologic findings in a patient with acute lymphocytic leukemia

We report a case of disseminated Trichosporon asahii in a patient on systemic antifungal therapy who presented with multiple cutaneous nodules suggestive of fungal infection. Histologic features resembled neutrophilic eccrine hidradenitis but staining with periodic acid‐Schiff and Gomori methenamine silver confirmed the clinical diagnosis. This case highlights the importance of maintaining suspicion for trichosporonosis and contextualizing histologic findings within the underlying clinical picture.     

Regional patterns of bone loss and altered bone remodeling in response to calcium deprivation in laboratory rabbits

Summary This study explores the effects of a calcium-deficient diet on patterns of bone remodeling, and examines regional differences in the amount of bone lost. Skeletally mature female rabbits (n=6) were fed a calcium-deficient diet (0.10% Ca²⁺ and 0.50% P) for 14 weeks. A separate group of rabbits (n=4) were fed a maintenance diet (1.2% Ca²⁺ and 0.45% P). Bone mineral content, serum calcium, and serum phosphorus were measured each week during the experimental period. Following sacrifice, the L₃ vetebra, femoral head, proximal tibial metaphysis, and tibial midshaft were analyzed histomorphometrically. Rabbits had 20% less vertebral bone after only 14 weeks of a calcium-deficient diet. As in human postmenopausal osteoporosis, bone loss in calcium-deficient rabbits occurs in the trabecular bone of the lumbar spine before that in the trabecular bone of the lower extremity. Calcium-deficient diets alone do not lead to increased osteoid volume or thickness. Because bone loss is relatively rapid and because the pattern of loss is similar in some respects to that found in humans, adult rabbits may provide an attractive model of calcium deficiency osteoporosis in a skeletally mature mammal in which remodeling is predominant over modeling.     

Cross-cultural invariance of the Academic Expectations Stress Inventory: Adolescent samples from Canada and Singapore

We provide further evidence for the two-factor structure of the 9-item Academic Expectations Stress Inventory (AESI) using confirmatory factor analysis on a sample of 289 Canadian adolescents and 310 Singaporean adolescents. Examination of measurement invariance tests the assumption that the model underlying a set of scores is directly comparable across groups. This study also examined the cross-cultural validity of the AESI using multigroup confirmatory factor analysis across both the Canadian and Singaporean adolescent samples. The results suggested cross-cultural invariance of form, factor loadings, and factor variances and covariances of the AESI across both samples. Evidence of AESI's convergent and discriminant validity was also reported. Findings from t-tests revealed that Singaporean adolescents reported a significantly higher level of academic stress arising from self expectations, other expectations, and overall academic stress, compared to Canadian adolescents. Also, a larger cross-cultural effect was associated with academic stress arising from other expectations compared with academic stress arising from self expectations.     

Evaluation of left ventricular mechanical dyssynchrony as determined by phase analysis of ECG-gated SPECT myocardial perfusion imaging in patients with left ventricular dysfunction and conduction disturbances

Background  Cardiac resynchronization therapy (CRT) is approved for the treatment of patients with advanced systolic heart failure and evidence of dyssynchrony on electrocardiograms. However, a significant percentage of patients do not demonstrate improvement with CRT. Echocardiographic techniques have been used for more accurate determination of dyssynchrony. Single photon emission computed tomography (SPECT) myocardial perfusion imaging has not previously been used to evaluate cardiac dyssynchrony. The objective of this study is to evaluate mechanical dyssynchrony as described by phase analysis of gated SPECT images in patients with left ventricular dysfunction, conduction delays, and ventricular paced rhythms. Methods and Results  A novel count-based method is used to extract regional systolic wall thickening amplitude and phase from gated SPECT images. Five indices describing the phase dispersion of the onset of mechanical contraction are determined: peak phase, phase SD, bandwidth, skewness, and kurtosis. These indices were determined in consecutive patients with left ventricular dysfunction (n=120), left bundle branch block (n=33), right bundle branch block (n=19), and ventricular paced rhythms (n=23) and were compared with normal control subjects (n=157). Phase SD, bandwidth, skewness, and kurtosis were significantly different between patients with left ventricular dysfunction, left bundle branch block, right bundle branch block, and ventricular paced rhythms and normal control subjects (all P<.001) Peak phase was significantly different between patients with right ventricular paced rhythms and normal control subjects (P=.001). Conclusions  A novel SPECT technique for describing left ventricular mechanical dyssyn-chrony has been developed and may prove useful in the evaluation of patients for CRT. This study was funded in part by a research grant from the Medtronic-Duke Strategic Alliance, of which Dr Borges-Neto is the primary investigator.     

A Comparison of Oral and Rectal Absorption of L-Dopa Esters in Rats and Mice

Short-chain alkyl esters of L-dopa were administered to rats and mice via oral and rectal routes. Plasma L-dopa esters and L-dopa were determined in the systemic and portal circulation by HPLC. A comparison of isopropyl, butyl, and 4-hydroxybutyl esters of L-dopa demonstrated significantly higher levels of the esters in both systemic and portal blood samples following rectal administration than following oral administration. In most cases, oral administration resulted in nondetectable (<0.01 µg/ml) levels of the esters in plasma. Correspondingly, the plasma levels of L-dopa itself were consistently higher following rectal administration. At very high oral doses (500 mg L-dopa equivalents/kg body weight), systemic plasma levels of the butyl ester could be detected (1.25 µg/ml at 10 min), which might indicate saturation of the esterase activity of the small intestine. These studies indicate that the systemic availability of L-dopa from short-chain alkyl esters of L-dopa may be best optimized by rectal administration, which avoids the relatively high esterase activity characteristic of the small intestine.     

Cleveland Clinic Lerner College of Medicine: an innovative approach to medical education and the training of physician investigators.

Cleveland Clinic Lerner College of Medicine (CCLCM) is an innovative, five-year medical education track within Case Western Reserve University School of Medicine (Case) with a focused mission to attract and educate a limited number of highly qualified persons who seek to become physician investigators. CCLCM curriculum governance, faculty appointments and promotions, and admissions committees are integrated with respective Case committees. The CCLCM curriculum is based on faculty-defined professional attributes that graduates are expected to develop. These attributes were used to create curricular and assessment principles that guided the development of an integrated basic science, clinical science, and research curriculum, conducted in an active learning environment. An organ-system approach is used to solidify an understanding of basic science discipline threads in the context of relevant clinical problems presented in PBL and case-based discussion formats. Clinical skills are introduced in the first year as part of the two-year longitudinal experience with a family practice or internal medicine physician. The research program provides all students with opportunities to learn and experience basic and translational research and clinical research before selecting a research topic for their 12- to 15-month master-level thesis project. All Case students participate in required and elective clinical curriculum after the second year, but CCLCM students return to the Cleveland Clinic on selected Friday afternoons for program-specific research and professionalism-learning activities. A unique portfolio-based assessment system is used to assess student achievements in nine competency areas, seven of which reflect the Accreditation Council for Graduate Medical Education competencies.     

Neuronal vacuole formation in the rat posterior cingulate/retrosplenial cortex after treatment with the N-methyl-d-aspartate (NMDA) antagonist MK-801 (dizocilpine maleate)

Cytoplasmic vacuoles appear in neurons of the posterior cingulate/retrosplenial cortex (PC/RS) of rats after treatment with N-methyl-d-aspartate (NMDA) receptor antagonists. Prominent dilatation of mitochondria and endoplasmic reticulum has been described within 2 h; however, the ultrastructural features of vacuole formation are unknown. To investigate this, the present study examined the PC/RS cortex of male rats (age 60–70 days) at 15, 30, 45, 60, 90, and 120 min after subcutaneous treatment with 1 mg/kg of the noncompetitive NMDA antagonist MK-801 (dizocilpine maleate, 5-methyl-10, 11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine). Subtle mitochondrial dilatation was identified in a few neurons as early as 15 min postdose (MPD). By 30 MPD, dilatation was more pronounced in mitochondria and also involved the endoplasmic reticulum and perinuclear space. Ribosomal disaggregation and degranulation were also evident by 30 MPD. At all subsequent time points, dilatation of mitochondria and endoplasmic reticulum progressed in severity. Although the relative involvement of mitochondria and endoplasmic reticulum varied, glia were not involved. These ultrastructural data suggest that after treatment with MK-801, mitochondrial dilatation precedes involvement of endoplasmic reticulum in vacuolization of susceptible PC/RS cortical neurons. The early mitochondrial effects identified in this study suggest an initial metabolic insult that rapidly progresses to affect endoplasmic reticulum and ribosomes. This strengthens the relationship between the ability of certain NMDA antagonists to induce energy perturbations and neuronal vacuoles in the same region of the rat cerebral cortex.     

Somatosensory evoked potentials are unchanged by reflex sympathetic dystrophy and by stellate ganglion block.

Median nerve somatosensory evoked potentials (SEPs) were monitored in patients with chronic pain before and after stellate ganglion blockade. A change caused by the syndrome or by the block would suggest that SEPs might be useful in the diagnosis and treatment of chronic pain. We observed 20 subjects. Group I (n = 10) had chronic pain not involving the upper extremity. Group II (n = 8) had reflex sympathetic dystrophy of the arm. All patients underwent unilateral stellate ganglion block using an anterior paratracheal approach. The SEPs were recorded by median nerve stimulation on the blocked (affected) side and unblocked (unaffected) side before and 30 min after the block. Recording sites were ipsilateral brachial plexus, the cervical spinal cord, and the contralateral sensory cortex. There were no between-group differences before or after the block. Paired analysis within each group showed that the SEPs were not different from baseline (unaffected side before block) at any time throughout the study. We conclude that since SEPs are not changed by the reflex sympathetic dystrophy or stellate ganglion block, they would not be useful in the evaluation of pain or in determining the effectiveness of sympathetic block. Both the pain and the block appear to involve alteration of conducting pathways separate from those monitored by median nerve SEPs.